Uses
1,3-Dichloro-2-nitrobenzene is an olfactory mucosa (OM) toxicants.Also, it is a starting material for 9-Chloro Quetiapine (C366040), which is an impurity of Quetiapine hemifumarate (Q510000), a dibenzothiazepine antipsychotic medication used in the treatment of schizophrenia.
Synthesis
2.1.5. Synthesis of 1,3-dichloro-2-nitrobenzene[4].
2,6-Dichloroaniline (8.10 g, 50.0 mmol) was dissolved in dichloromethane (200 mL) and the solution was cooled to 0 °C. A solution of 3-chloroperbenzoic acid (24.6 g, 100 mmol) in dichloromethane (250 mL) was slowly added dropwise at 0 °C for a controlled time of 1.5 hours. After the dropwise addition, the reaction mixture was continued to be stirred at room temperature for 2 hours. Subsequently, the reaction mixture was diluted with dichloromethane (250 mL). The reaction mixture was washed sequentially with 2 wt% aqueous sodium thiosulfate (2 x 100 mL), aqueous sodium bicarbonate (4 x 50 mL) and deionized water (200 mL). The organic layer was dried with magnesium sulfate and concentrated under reduced pressure to remove the solvent. The residue was suspended in n-hexane (40 mL), sonicated for 5 min and filtered, and the filter cake was washed with n-hexane (2 x 20 mL) to afford 1,3-dichloro-2-nitrobenzene (6.63 g, 37.7 mmol, 75% yield) as a beige solid.
References
[1] Patent: US2014/163256, 2014, A1. Location in patent: Paragraph 0161-0162
[2] Tetrahedron Letters, 1983, vol. 24, # 14, p. 1505 - 1508
[3] Tetrahedron, 1987, vol. 43, # 8, p. 1753 - 1758
[4] Beilstein Journal of Organic Chemistry, 2017, vol. 13, p. 768 - 778
[5] Journal of Medicinal Chemistry, 1968, vol. 11, # 4, p. 814 - 819
